The objective of this project is to integrate metabolic and physiologic MR imaging data into the clinical management of patients with newly diagnosed glioblastoma multiforme (GBM). Our current studies have provided strong evidence that Magnetic Resonance Spectroscopic Imaging (MRSI), Perfusion Weighted imaging (PWI) and Diffusion Weighted Imaging (DWI) produce information concerning the biological behavior of such lesions that is likely to be valuable for clinical decision making. We propose to explore the clinical impact of these imaging methods with respect to improving and evaluating treatment with Convection Enhanced Delivery (CED) of biologically active agents. The first area that is of interest is to more reliably identify the location of residual disease after surgery so that it will ultimately be possible to direct therapy to to foci of residual disease. The second area of interest is in defining metabolic and physiologic imaging parameters that predict whether the patient is likely to benefit from treatment that uses CED. The third area is in evaluating short-term changes that occur as a result of combining CED with subsequent radiation and chemotherapy. Previous studies of such focal treatments have not utilized state of the art metabolic and physiologic imaging methods to select patients, to identify microscopic disease and heterogeneity or to evaluate response to therapy. We believe that it is critical to determine whether this approach is feasible with regard to CED and to obtain evidence that would help in deciding how to best integrate such information into future clinical trials. Specific Aim 1 will provide direct correlation between specific imaging and tissue characteristics by immunohistochemical and ex-vivo NMR spectroscopy of image guided surgical samples from patients with newly diagnosed GBM. This will establish the link between in vivo MR parameters and biological behavior as defined by molecular morphology. Specific Aim 2 will address the characteristics of patients who are participating in a Phase II clinical trial of GBM patients receiving CED. It will examine the relationship between pre-CED MR parameters and subsequent imaging change, as well as comparing these findings with a population of patients with similar characteristics who have not been treated with CED.Specific Aim 3 will perform a Phase I clinical trial in patients with GBM that integrates the metabolic and physiologic imaging parameters that have been shown relevant with results obtained in Project 3 with regard to improving the CED process to more accurately target regions of interest. While the focus in these initial clinical trials is on patients who have received a gross total resection based on conventional MR imaging, the knowledge that will be gained has broad implications for selecting and targeting many other types of focal therapy and is likely to change the definition of tumor burden and response to therapy for patients with GBM